A wide range of mechanistic anti-viral assays has been developed and validated. The assay systems have facilitated the biological characterization of new lead compounds initially identified using the NCI primary anti-HIV screen. The assays define specific stages in the HIV life cycle and include a diverse set of biochemical endpoints. In addition, a comprehensive panel of human target cells and HIV strains has been established and standardized. The panel, which includes normal target cells and clinical isolates of HIV, is used to determine the biological range of activity of new lead compounds. Implementation of these assays has facilitated the prioritization of new lead synthetic compounds as well as natural product-derived compounds for preclinical development. During the present report year we have focused particularly upon novel natural product derived compounds.